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Information on EC 2.4.1.109 - dolichyl-phosphate-mannose-protein mannosyltransferase and Organism(s) Homo sapiens and UniProt Accession Q9UKY4
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2.4.1.109 dolichyl-phosphate-mannose-protein mannosyltransferaseIUBMB Comments
The enzyme transfers mannosyl residues to the hydroxy group of serine or threonine residues, producing cell-wall mannoproteins. It acts only on long-chain alpha-dihydropolyprenyl derivatives, larger than C35.
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Word Map
- 2.4.1.109
- muscular
- dystrophy
-
o-mannosylation
-
walker-warburg
- alpha-dystroglycan
- pomgnt1
-
o-glycosylation
-
fukutin
- muscle-eye-brain
- dystroglycanopathies
-
dystroglycan
-
girdle
-
alpha-dystroglycanopathy
- lissencephaly
-
fukuyama
-
hypoglycosylation
-
limb-girdle
-
alpha-dg
-
pomts
-
cobblestone
- heterotopia
-
fukutin-related
- medicine
- gmppb
-
o-mannose
- agriculture
- diagnostics
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
+
=
+
+
=
+
Synonyms
pomt1, pomt2, protein o-mannosyltransferase, pmt1p, o-mannosyltransferase, protein o-mannosyltransferase 1, pmt2p, pmt1p-pmt2p, pmt4p, aapmta, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dolichol phosphomannose-protein mannosyltransferase
-
-
-
-
mannosyltransferase, dolichol phosphomannose-protein
-
-
-
-
POMT1
POMT2
protein O-D-mannosyltransferase
-
-
-
-
protein O-mannosyltransferase 1
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexosyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
dolichyl-phosphate-D-mannose:protein O-D-mannosyltransferase
The enzyme transfers mannosyl residues to the hydroxy group of serine or threonine residues, producing cell-wall mannoproteins. It acts only on long-chain alpha-dihydropolyprenyl derivatives, larger than C35.
CAS REGISTRY NUMBER
COMMENTARY
74315-99-4
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dolichyl beta-D-mannosyl phosphate + synthetic peptide based on a mucin-like domain in alpha-dystroglycan
?
-
-
-
-
?
dolichyl phosphate D-mannose + alpha-dystroglycan glutathione-S-transferase fusion protein
dolichyl phosphate + O-D-mannosyl-[alpha-dystroglycan]
sugar donor tritium-labeled
-
-
?
dolichyl phosphate D-mannose + glutathione-S-transferase fusion alpha-dystroglycan
dolichyl phosphate + O-D-mannosyl-glutathione-S-transferase fusion alpha-dystroglycan
-
-
-
-
?
dolichyl phosphate D-mannose + glutathione-S-transferase fusion alpha-dystroglycan
dolichyl phosphate + O-D-mannosyl-[alpha-dystroglycan]
-
tritium-labeled sugar donor, 20 mM Tris-HCl, pH 8.0, 2-mercaptoethanol, EDTA, n-octyl-beta-D-thiogucoside, 22°C
-
-
?
dolichyl phosphate D-mannose + glutathione-S-transferase fusion alpha-dystroglycan
dolichyl phosphate + O-D-mannosyl-[glutathione-S-transferase fusion alpha-dystroglycan]
-
-
-
-
?
dolichyl phosphate D-mannose + N-acetyl-SSSSS
dolichyl phosphate + O-D-mannosyl-N-acetyl-SSSSS
-
worst substrate
-
-
?
dolichyl phosphate D-mannose + N-acetyl-YASAV
dolichyl phosphate + O-D-mannosyl-N-acetyl-YASAV
-
-
-
-
?
dolichyl phosphate D-mannose + N-acetyl-YATAV
dolichyl phosphate + O-D-mannosyl-N-acetyl-YATAV
-
best substrate
-
-
?
dolichyl phosphate D-mannose + N-acetyl-YATAVK-biotin
dolichyl phosphate + O-D-mannosyl-N-acetyl-YATAVK-biotin
-
N-acetyl-YATAVK-biotin preferentially reacts with isoform Pmt1p
-
-
?
dolichyl phosphate D-mannose + protein
dolichyl phosphate + O-D-mannosylprotein
-
catalyzes the initial step of O-mannosyl glycan biosynthesis
-
-
?
dolichyl phosphate D-mannose + protein
dolichyl phosphate + O-D-mannosylprotein
-
synthetic peptides based on a mucin-like domain in alpha-dystroglycan. Thr414 of peptide 401-420 and Thr351 of peptide 336-355 are prominently modified by O-mannosylation
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dolichyl phosphate D-mannose + protein
dolichyl phosphate + O-D-mannosylprotein
-
catalyzes the initial step of O-mannosyl glycan biosynthesis
-
-
?
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.63
synthetic peptide based on a mucin-like domain in alpha-dystroglycan
-
25°C, pH 8.0
-
0.73
synthetic peptide based on a mucin-like domain in alpha-dystroglycan
-
25°C, pH 8.0
-
2.96
synthetic peptide based on a mucin-like domain in alpha-dystroglycan
-
25°C, pH 8.0
-
2.98
synthetic peptide based on a mucin-like domain in alpha-dystroglycan
-
25°C, pH 8.0
-
9.7
synthetic peptide based on a mucin-like domain in alpha-dystroglycan
-
25°C, pH 8.0
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
lymphoblast-based enzymatic assays are accurate and useful methods to select patients harbouring POMT1 and POMT2 mutations among those with a suspected or confirmed alpha-dystroglycanopathy
of brain with subarachnoid spread. Distinct POMT1 alterations may contribute to a functional impairment of protein-omannosyltransferase activity. In individual tumor specimens selective alterations of the POMT1 gene may be compatible with clonal evolution of distinct sublocations
lymphoblast-based enzymatic assays are accurate and useful methods to select patients harbouring POMT1 and POMT2 mutations among those with a suspected or confirmed alpha-dystroglycanopathy
with subarachnoid spread. Distinct POMT1 alterations may contribute to a functional impairment of protein-O-mannosyltransferase activity. In individual tumor specimens selective alterations of the POMT1 gene may be compatible with clonal evolution of distinct sublocations
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
malfunction
dystroglycanopathies (muscular dystrophy due to abnormal glycosylation of alpha-dystroglycan) such as the severe Walker-Warburg syndrome (brain and eye abnormalities, mild limb girdle muscular dystrophy)
malfunction
-
mutation in either one of the complex forming enzymes can lead to Walker-Warburg syndrome, a congenital muscular dystrophy with abnormal neuronal migration
metabolism
-
a complex of protein O-mannosyltransferase 1 and 2 catalyzes the initial step of O-mannosyl glycan biosynthesis
metabolism
-
isoforms POMT1 and POMT2 catalyze the initial step of O-mannosyl glycan biosynthesis
metabolism
-
protein O-mannosyltransferase 1 (POMT1) and its homolog, POMT2, are responsible for the catalysis of the first step in O-mannosyl glycan synthesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). POMT2_HUMAN
750
10
84214
Swiss-Prot
Mitochondrion (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
71000
limb girdle muscular dystrophy deletion mutant p.A589VfsX38 enzyme, Western blot analysis, SDS-PAGE with antibody staining
73000
-
rough estimate from SDS-PAGE figure, fully glycosylated enzyme, 2-3 kDa lower than wild-type corresponds to lack of a single N-glycan chain
85000
additional information
85000
limb girdle muscular dystrophy mutant L171A enzyme, Western blot analysis, SDS-PAGE with antibody staining
85000
wild-type enzyme, Western blot analysis, SDS-PAGE with antibody staining
additional information
Walker-Warburg syndrome p.del77-93 mutant enzyme is not detectable, Western blot analysis, SDS-PAGE with antibody staining
additional information
-
Walker-Warburg syndrome p.del77-93 mutant enzyme is not detectable, Western blot analysis, SDS-PAGE with antibody staining
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
POMT1, 3 of 4 potential glycosylation sites, inhibition of glycosylation with tunicamycin inactivates enzyme, mutation of all sites prevents solubilization of the enzyme
glycoprotein
-
POMT2, all of 5 potential glycosylation sites, inhibition of glycosylation with tunicamycin inactivates enzyme, mutation of all sites prevents solubilization of the enzyme
glycoprotein
-
three of the four POMT1 sites (Asn435, Asn471 and Asn539) and all five of the POMT2 N-glycosylation sites (Asn98, Asn330, Asn445, Asn528 and Asn583) are N-glycosylated
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D77A/E78A
D77A/E78A/D92A/E93A
-
the PMT1/PMT2 mutant shows 0.24% activity compared to the wild type enzyme
D80E/E81D
-
the PMT4 mutant shows 116.54% activity compared to the wild type enzyme
D92A/E93A
-
the PMT2 mutant shows 3.63% activity compared to the wild type enzyme
L171A
stable enzyme with reduced activity causing phenotype limb girdle muscular dystrophy 2K, together with partial heterozygous deletion p.A589VfsX38 mutant, reduced amounts of O-mannosyl linked glyco-epitope (IIH6) on alpha-dystroglycans resulting in less than 100-125 kDa alpha-dystroglycans, about 40% residual enzyme activity
N16Q
N16Q/N435Q/N471Q/N539Q
N330Q
-
2-3 kDa smaller than wild-type corresponding to single N-glycan chain, single mutation with no effect on activity
N435Q
N445Q
N471Q
N528Q
N539Q
N583Q
N98Q
N98Q/N330Q/N445Q/N528Q/N583Q
additional information
D77A/E78A
-
the PMT1 mutant shows 0.19% activity compared to the wild type enzyme
D77A/E78A
-
the PMT1 mutant shows 3.59% activity compared to the wild type enzyme
N16Q
-
not smaller than wild-type, may be too close to membrane for a glycosylation site, single mutation with about 70% of wild-type activity
N16Q/N435Q/N471Q/N539Q
-
together with POMT2 mutant N98Q/N330Q/N445Q/N528Q/N583Q, significantly lower activity than double wild-type, a lack of glycosylation prevents solubilization
N16Q/N435Q/N471Q/N539Q
-
together with wild-type POMT2, significantly lower activity than double wild-type, a lack of glycosylation prevents solubilization
N435Q
-
2-3 kDa smaller than wild-type corresponding to single N-glycan chain, single mutation with about 70% of wild-type activity
N445Q
-
2-3 kDa smaller than wild-type corresponding to single N-glycan chain, single mutation with no effect on activity
N471Q
-
2-3 kDa smaller than wild-type corresponding to single N-glycan chain, single mutation with about 70% of wild-type activity
N528Q
-
2-3 kDa smaller than wild-type corresponding to single N-glycan chain, single mutation with no effect on activity
N539Q
-
2-3 kDa smaller than wild-type corresponding to single N-glycan chain, single mutation with no effect on activity
N583Q
-
2-3 kDa smaller than wild-type corresponding to single N-glycan chain, single mutation with no effect on activity
N98Q
-
2-3 kDa smaller than wild-type corresponding to single N-glycan chain, single mutation with about 50% of wild-type activity
N98Q/N330Q/N445Q/N528Q/N583Q
-
together with POMT1 mutant N16Q/N435Q/N471Q/N539Q, significantly lower activity than double wild-type, a lack of glycosylation prevents solubilization
N98Q/N330Q/N445Q/N528Q/N583Q
-
together with wild-type POMT1, significantly lower activity than double wild-type, a lack of glycosylation prevents solubilization
additional information
heterozygous deletion leading to a frame shift mutation causing an amino acid exchange A589V and a premature stop codon after 38 amino acids (p.A589VfsX38), reduced enzyme stability, reduced amounts of O-mannosyl linked glyco-epitope (IIH6) on alpha-dystroglycans resulting in less than 100-125 kDa alpha-dystroglycans, about 40% residual enzyme activity, phenotype limb girdle muscular dystrophy 2K
additional information
-
heterozygous deletion leading to a frame shift mutation causing an amino acid exchange A589V and a premature stop codon after 38 amino acids (p.A589VfsX38), reduced enzyme stability, reduced amounts of O-mannosyl linked glyco-epitope (IIH6) on alpha-dystroglycans resulting in less than 100-125 kDa alpha-dystroglycans, about 40% residual enzyme activity, phenotype limb girdle muscular dystrophy 2K
additional information
-
single site mutations defective in potential glycosylation sites do not change enzyme activity, mutaions of all such sites cause a loss of enzyme activity, probably due to decreased hydrophilicity
additional information
-
single site mutations defective in potential glycosylation sites do not change enzyme activity, mutations of all such sites cause a loss of enzyme activity, probably du to decreased hydrophilicity
additional information
-
mutations of all N-glycosylation sites of either isoform POMT1 or POMT2 cause a loss of enzyme activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
isolation of microsome fraction: cells are homogenized in 10 mM Tris-HCl, pH 7.4, EDTA, sucrose, DTT, protease inhibitors, centrifugation, supernatant ultracentrifuged, precipitate used as microsomal fraction, solubilized in 20 mM Tris-HCl, pH 8.0, 2-mercaptoethanol, EDTA, n-octyl-beta-D-thioglucoside, centrifugation, supernatant used as solubilized microsome preparation, separation with SDS-PAGE and antibody staining
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
transfection of expression plasmids with wild-type and mutant enzyme variants into HEK-293T cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
POMT2 mutations in patients with congenital muscular dystrophy (Italian population)
diagnostics
analysis of fibroblasts to elucidate the phenotypes of POMT1 mutations
medicine
POMT1 mutations in patients with congenital muscular dystrophy (Italian population)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Manya, H.; Suzuki, T.; Akasaka-Manya, K.; Ishida, H.K.; Mizuno, M.; Suzuki, Y.; Inazu, T.; Dohmae, N.; Endo, T.
Regulation of mammalian protein O-mannosylation: Preferential amino acid sequence for O-mannose modification
J. Biol. Chem.
282
20200-20206
2007
Homo sapiens
Manya, H.; Bouchet, C.; Yanagisawa, A.; Vuillaumier-Barrot, S.; Quijano-Roy, S.; Suzuki, Y.; Maugenre, S.; Richard, P.; Inazu, T.; Merlini, L.; Romero, N.B.; Leturcq, F.; Bezier, I.; Topaloglu, H.; Estournet, B.; Seta, N.; Endo, T.; Guicheney, P.
Protein O-mannosyltransferase activities in lymphoblasts from patients with alpha-dystroglycanopathies
Neuromuscul. Disord.
18
45-51
2008
Homo sapiens (Q9UKY4), Homo sapiens (Q9Y6A1), Homo sapiens
Messina, S.; Mora, M.; Pegoraro, E.; Pini, A.; Mongini, T.; DAmico, A.; Pane, M.; Aiello, C.; Bruno, C.; Biancheri, R.; Berardinelli, A.; Boito, C.; Farina, L.; Morandi, L.; Moroni, I.; Pezzani, R.; Pichiecchio, A.; Ricci, E.; Ruggieri, A.; Saredi, S.; Scuderi, C.; Tessa, A.; Toscano, A.; Tortorella G; Trevisan C.P.; Uggetti C.; Santorelli F.M.; Bertini E.; Mercuri E.
POMT1 and POMT2 mutations in CMD patients: a multicentric Italian study
Neuromuscul. Disord.
18
565-571
2008
Homo sapiens (Q9UKY4), Homo sapiens (Q9Y6A1), Homo sapiens
Snoei, J.; Urbach, H.; Engels, G.; Fassunke, J.; von Lehe, M.; Becker, A.J.; Majores, M.
Genetic alterations of protein-o-mannosyltransferase-1 in glioneuronal and glial brain tumors with subarachnoid spread
Neuropathology
29
116-124
2009
Homo sapiens (Q9Y6A1), Homo sapiens
Manya, H.; Akasaka-Manya, K.; Nakajima, A.; Kawakita, M.; Endo, T.
Role of N-glycans in maintaining the activity of protein O-mannosyltransferases POMT1 and POMT2
J. Biochem.
147
337-344
2009
Homo sapiens
Lommel, M.; Cirak, S.; Willer, T.; Hermann, R.; Uyanik, G.; van Bokhoven, H.; Koerner, C.; Voit, T.; Bari?, I.; Hehr, U.; Strahl, S.
Correlation of enzyme activity and clinical phenotype in POMT1-associated dystroglycanopathies
Neurology
74
157-164
2010
Homo sapiens (Q9Y6A1), Homo sapiens
Akasaka-Manya, K.; Manya, H.; Hayashi, M.; Endo, T.
Different roles of the two components of human protein O-mannosyltransferase, POMT1 and POMT2
Biochem. Biophys. Res. Commun.
411
721-725
2011
Homo sapiens
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